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Cerebral IRI models were established by oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) and middle cerebral artery occlusion (MCAO). 2,3,5\u2010Triphenyltetrazolium chloride (TTC) staining was utilized to detect cerebral infarct size and mNSS was performed to evaluate neurologic deficits. Brain pathologic changes were analyzed by HE staining. Lipid peroxidation level was detected by C11\u2010BODIPY staining, and Fe<jats:sup>2+<\/jats:sup> and MDA levels were measured using the kits. Cell vitality was examined by CCK\u20108 assay. Dual\u2010luciferase reporter and ChIP assays were adopted to determine the interaction between SOX9 and DMT1 promoter. Dex ameliorated ferroptosis and neuronal death induced by MCAO and OGD\/R. SOX9 upregulation abolished the inhibitory effect of Dex on OGD\/R\u2010induced ferroptosis and neuronal death in SH\u2010SY5Y cells. Our further trials showed that SOX9 transcriptionally activated DMT1 expression. As expected, DMT1 overexpression prevented Dex\u2010induced decrease in ferroptosis and neuronal death in OGD\/R\u2010treated SH\u2010SY5Y cells. Dex inhibited ferroptosis to exert neuroprotection effects on cerebral IRI by inactivating the SOX9\/DMT1 axis.<\/jats:p>","DOI":"10.1111\/cbdd.70022","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T05:13:33Z","timestamp":1736140413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Dexmedetomidine Inhibits Ferroptosis by Regulating the SRY\u2010Box Transcription Factor 9\/Divalent Metal Transporter\u20101 Axis to Alleviate Cerebral Ischemia\/Reperfusion Injury"],"prefix":"10.1111","volume":"105","author":[{"given":"Zhen","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qionghua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of 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